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目的探讨α-硫辛酸对糖尿病大鼠血糖、血脂及肝脏内腺苷酸活化蛋白激酶(Adenosine monophosphate activated protein kinase,AMPK)α亚基(AMPKα)表达及活性的影响。方法应用高脂饮食联合腹腔单次注射小剂量的链脲佐菌素(STZ)复制2型糖尿病合并脂代谢紊乱的Wistar大鼠模型,再将模型大鼠随机分为糖尿病对照(DC)组和α-硫辛酸治疗(LA)组,并设正常对照(NC)组。NC组和DC组每只给予生理盐水2ml/d,LA组经腹腔注射α-硫辛酸60mg/kg·d,共4周。分别测定各组大鼠的体重、血糖、血脂、糖化血红蛋白(HbA1c)和肝脏内AMPKα及磷酸化AMPKα(pAMPKα)的表达水平。结果建模后、给药前及给药后,NC组大鼠血糖水平均显著低于DC和LA组(P<0.01),给药后,LA组显著低于DC组(P<0.05)。给药4周后,DC组大鼠甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白(LDL)和HbA1c水平均显著高于NC组(P<0.01),而高密度脂蛋白(HDL)、肝脏内AMPKα及pAMPKα的表达水平均显著降低(P<0.05);LA组大鼠TG、TC、LDL和HbA1c水平均较DC组显著下降(P<0.05),而HDL、AMPKα及pAMPKα表达水平均显著升高(P<0.05);DC组肝脏内AMPKα表达较NC组明显下降(P<0.05),LA组无明显变化(P>0.05)。结论α-硫辛酸可以通过调节肝脏内AMPKα的表达水平,进而改善糖尿病状态下的“糖脂毒性”。
Objective To investigate the effects of α-lipoic acid on blood glucose, blood lipid and AMPKα expression and activity in liver of diabetic rats. Methods Wistar rats with type 2 diabetes mellitus complicated with lipid metabolism were duplicated with high fat diet and single intraperitoneal injection of streptozotocin (STZ). The rats were randomly divided into diabetic group (DC) and control group α-lipoic acid (LA) group and normal control (NC) group. NC group and DC group were given normal saline 2ml / d, LA group by intraperitoneal injection of α-lipoic acid 60mg / kg · d, a total of 4 weeks. The body weight, blood glucose, blood lipids, HbA1c and the expression of AMPKα and pAMPKα in the liver of the rats in each group were measured. Results After modeling, the blood glucose levels in NC group were significantly lower than those in DC and LA groups before and after administration (P <0.01). After administration, LA group was significantly lower than DC group (P <0.05). After 4 weeks of administration, the levels of triglyceride (TG), total cholesterol (TC), low density lipoprotein (LDL) and HbA1c in DC group were significantly higher than those in NC group (P <0.01) (P <0.05). The levels of TG, TC, LDL and HbA1c in HD group were significantly lower than those in DC group (P <0.05), while the expressions of HDL, AMPKα, (P <0.05). The expression of AMPKα in liver of DC group was significantly lower than that of NC group (P <0.05), but there was no significant change in LA group (P> 0.05). Conclusion α-lipoic acid can regulate the expression of AMPKα in the liver and then improve the “glycolipid toxicity” in the diabetic state.